链球菌燃烧性外毒素B分裂GSDMA并触发燃烧性死亡
Wanyan Deng1,2,3, Yang Bai1,4, Fan Deng1,4
1The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Nature
|February 3, 2022
概括
来自Streptococcus pyogenes的细菌SpeB蛋白酶可以分裂气体皮质A (GSDMA),从而启动热. 这种GSDMA激活对宿主防御这种危险的皮肤病原体至关重要.
科学领域:
- 免疫学
- 微生物学
- 细胞生物学
背景情况:
- 气体皮质 (GSDMA-GSDME) 是形成孔隙的蛋白质,是炎症性细胞死亡机制的核心.
- 虽然已知GSDMB-E的激活剂,但GSDMA在皮肤中普遍存在的激活途径尚不清楚.
- 链球菌 (Streptococcus pyogenes) 是一种重要的细菌皮肤病原体.
研究的目的:
- 阐明GSDMA被激活的机制.
- 调查GSDMA对宿主感染的防御作用.
主要方法:
- 在体外测定GSDMA的SpeB蛋白酶活性.
- 分析GSDMA裂痕部位和所产生的碎片.
- 在角质细胞中诱导热的评估.
- 在感染GAS的Gsdma1缺陷小鼠中评估宿主免疫反应.
主要成果:
- GAS 囊蛋白酶 SpeB 在 Gln246 分裂 GSDMA,生成一个活跃的 N-终端片段.
- 这种裂变事件触发了角质细胞的灭.
- 缺乏Gsdma1的小鼠对GAS的免疫反应受损,导致细菌的扩散和死亡率增加.
- GSDMA 作为 SpeB 的传感器和基质,从而启动热.
结论:
- 通过GAS SpeB激活GSDMA提供了控制这种病原体的直接宿主机制.
- 这一途径突显了GSDMA在皮肤免疫力和宿主防御细菌感染中的关键作用.
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